There’s no room for guesswork in medicine. In order for CBD-based treatments to catch on among health professionals as a go-to prescription for pain relief and other afflictions, health professionals need to be sure that the product can be administered in a way that is precise. This is why technologies that allow health professionals to know accurately how much CBD is making it into the brains of their patients are a critical step in the development of cannabinoid-based medicine.
PreveCeutical Medical (CSE:PREV, OTCQB:PRVCF, FSE:18H) is one of the companies looking to answer that question. The company is developing a Sol-gel system for slow, controlled CBD release directly from nose to brain, bypassing the bloodstream and ensuring that the cannabinoids are not broken down before delivery to the brain. As an example of cannabis delivery systems, the Sol-gel technology enters the nose as a liquid but turns to gel upon contact with mucosal tissue and slowly releases a steady dose for up to seven days.
With more and more jurisdictions allowing CBD every year, either through wider cannabis legislation or as exemptions to anti-cannabis laws, CBD is making incredible headway towards mainstream medical acceptance. At this point, one of the top considerations for this drug is how best to deliver it in a way that is efficient, predictable and reliable.
One of the biggest developments and innovations to come out of the recent renaissance of cannabinoid based medicine has been the popularization of CBD. For many sufferers of chronic pain and other debilitating conditions who have found relief in medicinal cannabis, CBD offers a solution to the question of what these people are supposed to do when they need that relief but also need to function in their day to day lives.
A few innovative CBD and cannabis delivery systems
If CBD is to be adopted by the mainstream medical community as a common prescription, the question of effective delivery needs to be answered.
Nanobiotechnology company NanoSphere Health Sciences (CSE:NSHS) is developing a technology that encases transdermally ingested cannabinoids in a phospholipid membrane very similar to the membranes that protect cells in the body, allowing them to pass through the bloodstream without being broken down. Swiss-based medical cannabis company Satipharm, owned by Canadian company Harvest One Cannabis (TSXV:HVT), has developed Gellpell® capsules that contain 2-millimeter-long gelatin beads containing concentrated cannabinoids. The capsules dissolve in the small intestine, distributing the gelatin beads and creating a micro-emulsion with a high level of bioavailability. Meanwhile, Lexaria Bioscience (CSE:LXX,OTCQB:LXRP) is working on technologies that improve the bioavailability of cannabinoids in cannabis-infused edibles.
Even when the dose being put into the body is measured with one hundred percent accuracy, it’s still difficult to account for what happens to the substance after it has been adjusted. Whether the product is inhaled, taken orally or taken topically, it still has to travel through the bloodstream before making it to the brain. As any substance passes through the bloodstream, it is broken down and stored in fat cells. This means that, using any of these conventional methods, the amount of CBD that actually makes it to the endocannabinoid system is much lower than the dosage taken.
Why we need cannabis delivery systems
Still, many health professionals remain wary about prescribing CBD medicine, and their reasoning stems in large part from a few unknowns in regards to how the drug should be taken and delivered.
In short, CBD is a chemical compound found in cannabis plants that has been proven to help the body regulate pain, inflammation, anxiety, stress and more. Unlike it’s cousin tetrahydrocannabinol (THC), CBD does not have a psychoactive effect, meaning that it can be used without getting high.
Their high lipophilicity and low stability (degradation via the effects of temperature, light and auto-oxidation can occur) mean that cannabinoids benefit greatly from nanotechnology approaches . Indeed, recent years have seen micellar, liposomal and nanosized formulations being proposed for use in topical and systemic preparations. A brief description of the approaches presented in patents and in the literature, follows, while principal formulation data are reported in Table 2 .
NLC have recently been proposed for administration as a dosage form for nasal delivery. Nanospheres of 200 nm diameter, composed of either cetyl palmitate or glyceryl dibehenate and loaded with THC were obtained. In vitro mucoadhesion evaluations have revealed that cationic NLC formulations (obtained via the addition of cetylpyridinium chloride) should have high mucoadhesiveness properties . The solid matrix of the NLC was found to have a stabilizing effect on THC. Indeed, 91% of the THC was unaltered after 6 months storage at 4 °C. About 1.7 mg THC is administered with one spray of the 0.25% THC-loaded NLC formulation in each nostril. This amount was close to the THC amounts obtained from the oromucosal formulation in a study by Johnson et al. .
Lipid nanoparticles in a solid particle matrix are produced from oil/water emulsions by simply replacing the liquid lipid (oil) with a solid lipid, i.e., one that is solid at body temperature. First generation analogues, produced from a solid lipid only, are named solid lipid nanoparticles. The second generation of nanostructured lipid carrier (NLC) particles are produced from a blend of a solid lipid and a liquid lipid, in which the partially crystallized lipid particles, with mean radii ≤ 100 nm, are dispersed in an aqueous phase containing one or more emulsifiers . NLC can be considered suitable carrier systems for THC and CBD because they make use of solid particle matrices instead of fluid matrices, such as emulsions and liposomes, meaning that NLC can better host substances and protect them from degradation. The solid particle matrix is also able to slow the diffusion of THC from inside the particle to the particle surface.
3.5.1. Lipid Carriers
Biocompatible polymer PLGA was preferred by Martin-Banderas for the preparation of THC-loaded nanoparticles for use as an anticancer agent . Nanoparticles, with sizes ranging from 290–800 nm, were obtained with PEG, chitosan and PEG-chitosan being used as coating agents. Encapsulation efficiency and drug loading (around 96% and 4.8%, respectively) were not affected by the type of coating used and sustained drug release, of up to 10 days, was obtained. Surface modification with PEG reduced protein adsorption and thus, most likely, the in vivo opsonisation processes.
CB2 is principally expressed in immune cells, but can also be found in various other cell types, including chondrocytes, osteocytes and fibroblasts, meaning that it can be considered the peripheral cannabinoid receptor. It is also present in some nervous tissues, such as dorsal root ganglia and microglial cells. CB2 shows 44% amino acid similarity with CB1, and similarly inhibits adenylate cyclase as well as activating mitogen-activated protein kinase. Moreover, CB2 activation can increase intracellular calcium levels via phospholipase C. While both CB1 and CB2 are coupled to G-proteins, the transduction pathways that they activate can be different, for example, in their interactions with ion channels . The association of a particular variant of CB2, known as Q63R, with coeliac disease, immune thrombocytopenic purpura and juvenile idiopathic arthritis is particularly interesting for the field of autoimmune and rheumatic diseases .
The endocannabinoid system’s contribution to the regulation of such a variety of processes makes phytocannabinoid pharmacological modulation a promising therapeutic strategy for many medical fields, including the studies of analgesic, neuroprotective, anti-inflammatory and antibacterial activity [13,14].
3.5.2. Polymeric Carriers
Polymers have played an integral role in the advancement of drug delivery technology and this field has grown tremendously. Polymers are currently used in pharmaceutical formulations and show a wide range of safety and biodegradation variables. Developments in responsive polymers, polymer therapeutics and advanced systems for molecular recognition or for the intracellular delivery of novel therapeutics have more recently appeared [135,136]. Polymeric drug delivery systems are able to protect drugs from degradation and control drug release.
Conclusions in studies into reducing opioid doses in the management of chronic pain, where some trials have shown clinical benefits, are sometimes not completely reliable as they inadequately report dose changes and have mixed results in analgesic effects . Recent analysis has found no evidence to suggest that Cannabis can exert an opioid-sparing effect .